The proposed investigation is a study of the interaction of cysteine analogs with the cysteine incorporation system of protein biosynthesis. In order to carry out this study, purification of the cysteinyl-RNA synthetase and the tRNA specific for cysteine will have to be accomplished. Purification of synthetases and tRNA's specific for certain other amino acids also may be necessary in order to determine if the recognition of a particular analog by an aminoacyl-RNA synthetase can be predicted from the structure of that analog. In addition, the mechanism of synthetase interaction with cysteine ATP and tRNA will be studied in detail. Both in vivo and in vitro studies will be made of important features concerned with the incorporation into protein of amino acid analogs, particularly those analogs of cysteine, and any effect they may have on the alteration of cellular metabolism. This investigation should provide a better understanding of the effect that amino acid analogs once incorporated into cellular proteins have in altering the normal functions of these proteins.